Recent advances in the understanding of the mechanism of allograft rejection and the ability to isolate large quantities of islets from human pancreas have resulted in renewed interest in islet transplantation as a cure for diabetes. Initial islet allografts in humans will likely be performed in patients having or receiving renal allografts. There is little information on the interaction of different allografts in the rejection process, especially when considering the role of dendritic cells. This proposal is a study of: (1) the interaction of the rejection of islets, kidney, skin and thyroid allografts in rats, and (2) the isolation of dendritic cells from each organ to directly explore their role in allograft rejection. This research will be essential in developing a rational regimen for human renal and islet transplantation and in understanding the mechanism of action of dendritic cells. The interaction of kidney, skin, thyroid and islet allografts will be explored by performing combinations of two organ transplants as an extension of our initial studies on the interaction of islet and thyroid allografts. Islets and thyroid allografts are used as examples of rejection initiated by class I MHC antigen, and skin and kidney are taken as examples of rejection initiated by class II antigen. The organ specificity of the dendritic cells in the interaction of allograft rejection will be determined by removal of dendritic cells from one of the combination of allograft i.e. islets, thyroid or skin. To further study the organ specificity and mechanisms of action of the dendritic cells, the dendritic cells will be isolated and purified from each organ by adaptation of differential adherence techniques. The organ specificity of the isolated dendritic cells will be determined by the effect of the dendritic cells on the initiation of rejection of a combination of established allografts. The information from these studies will be important to develop rational approaches to combinations of renal and islet transplantation as it applies to human islet transplantation for the cure of diabetes and in understanding the role of dendritic cells on that process. The studies will be the basis for additional study on the control and regulation of the dendritic cells.